Igd Class Switch Recombination Is Not Controlled Through the Immunoglobulin Heavy Chain 3&Prime

Total Page:16

File Type:pdf, Size:1020Kb

Igd Class Switch Recombination Is Not Controlled Through the Immunoglobulin Heavy Chain 3&Prime Cellular & Molecular Immunology (2017) 14, 871–874 & 2017 CSI and USTC All rights reserved 2042-0226/17 $32.00 www.nature.com/cmi LETTER TO THE EDITOR IgD class switch recombination is not controlled through the immunoglobulin heavy chain 3′ regulatory region super-enhancer Hussein Issaoui1, Nour Ghazzaui1, Alexis Saintamand2, Yves Denizot and François Boyer Cellular & Molecular Immunology (2017) 14, 871–874; doi:10.1038/cmi.2017.81; published online 4 September 2017 n secondary lymphoid organs, mature enigmatic event restricted to a few B-cell 3’RR-deficient mouse B cells were used IB cells express membrane immuno- subsets in specific lymphoid tissues (such for these experiments. In some experi- globulin (Ig) of M and D isotypes (IgM as mesenteric lymph nodes, peritoneal ments, 3′RR-deficient mice were and IgD, respectively) of the same spe- cavity and mucosa-associated tissue) in pristane-treated (1 ml) for 2 months to cificity through alternative splicing of a both mice and humans.3–5 A recent induce inflammation prior to the recov- pre-mRNA encompassing the VDJ vari- study suggested that IgD CSR is initiated ery of peritoneal cavity cells. As pre- 5 4 able region and Cμ and Cδ heavy chain by microbiota, demonstrating a role for viously described in detail, junctions constant exons.1 After encountering anti- IgD in the homeostatic regulation of the were amplified using touchdown PCR gen, B cells undergo class switch recom- microbial community. The mechanistic followed by nested PCR. Libraries of bination (CSR) by which the Cμ gene is regulation of IgD CSR remains enig- 200 bp were prepared from the 1–2kb substituted with Cγ, Cε or Cα, thereby matic, reflecting the difficulty to obtain PCR products of Sμ–σδ amplification for generating IgG, IgE and IgA antibodies asufficient number of Sμ–σδ (σ for ion proton sequencing (‘GénoLim plat- of the same antigenic specificity but with S-like) junction sequences for molecular form’ of the Limoges University, France). new effector functions. CSR requires the analysis. We recently reported a new Sequenced reads were subsequently DNA-editing enzyme activation-induced computational tool (CSReport) for the mapped to Sμ and σδ regions using the deaminase (AID), which targets switch automatic analysis of CSR junctions BLAST algorithm. The computational (S) regions preceding Cμ (namely, the Sμ sequenced using high-throughput tool developed for experiments performs 6 fi donor region) and Cγ, Cε and Cα genes sequencing, and we used this tool to junction assembly, identi es break points 1 –σ wt σ fi (namely, the Sγ,ε,α acceptor regions). analyze Sμ δ junctions in wild-type ( ) in Sμ and δ,identies junction struc- CSR is controlled in trans through a mice.7 Genomic deletion of the 3′RR tures (blunt, micro-homology or junc- wide spectrum of enzymes and proteins super-enhancer abrogates CSR to IgG, tions with insertions) and outputs a 2,8 and in cis through the immunoglobulin IgE and IgA classes. In contrast, a statistical summary of the identified heavy chain (IgH) 3′ regulatory region unique study, based on the analysis of a junctions. (3′RR) super-enhancer that specifically few Sμ–σδ junctions, reported the 3′RR In 3′RR-deficient mice, among 4 904 AID-poises the S acceptor but not the Sμ super-enhancer as dispensable for IgD 163 raw reads, 39 046 reads were 4 donor region.2 IgD CSR is a rare and CSR. We thus used CSReport and high- mapped to a switch junction, and the throughput sequencing to conduct a presence of 190 unique Sμ–σδ junctions UMR CNRS 7276, University of Limoges, CBRS, more in depth analysis of Sμ–σδ junc- was documented. The number of unique 87025 Limoges, France. tions in 3′RR-deficient mice. junctions (that is, clonally independent) 1These authors contributed equally to this work. 2Present address: INSERM U1236, Université The present study was approved by was indeed dependent on the biological Rennes 1, Rennes, France. our local ethics committee review board frequency of this CSR event in the Correspondence: Dr Y Denizot, PhD, UMR CNRS (Comité Régional d'Ethique sur l'Expéri- studied samples. Compared to previous 7276, University of Limoges, CBRS, Rue Pr. mentation Animale du Limousin, studies of other IgD7 and IgG6 junctions Descottes, 87025 Limoges, France. wt E-mail: [email protected] Limoges, France) and conducted accord- in animals, IgD CSR clearly appears as Received: 13 July 2017; Revised: 17 July 2017; ing to the European guidelines for ani- a rare event. The structural profiles of Accepted: 18 July 2017 mal experimentation. Peritoneal cavity IgD junctions (blunt, micro-homology 3'RR independent IgD CSR HIssaouiet al 872 or junction with insertions) in 3′RR- The frequency of DNA breaks in Sμ was are reported in Figure 1c (left panel). deficient mice are reported in Figure 1a significantly elevated in AGCT sites com- The breaks detected in the σδ region did (left panel). The positions of IgD junc- pared to the frequency of theoretical not show a significant AID signature, tions in terms of distance from the random breaks. The positions of IgD with most of the break points observed forward PCR primer in Sμ and the junctions in terms of distance from the outside AID motifs. Pristane injection localization of IgD junctions with reverse PCR primer in σδ and the increased the frequency of IgH/c-myc WRCY, RGYW, AGCT and GGG motifs localizations of IgD junctions with translocations; most of the IgH breaks are reported in Figure 1b (left panel). WRCY, RGYW, AGCT and GGG motifs occurred in the Sμ region. We thus used Cellular & Molecular Immunology 3'RR independent IgD CSR HIssaouiet al 873 Figure 1 Quantitative description of Sμ–σδ junctions using CSReport workflow. Left panel: results from pooled peritoneal B cells obtained from 30 3′RR-deficient mice. Right panel: results from pooled peritoneal B cells from seven 3′RR-deficient mice treated with 1 ml of pristane for 2 months. (a) Structure profiles of Sμ–σδ junctions. Junctions are classified in terms of junction types (junction with insertions, blunt junction or junction with micro-homology) and size (in bp of insertions or micro-homologies). The number in parentheses indicates the number of junctions of each type. The junction profile is significantly different (P = 0.0005, Fisher’s exact test) under basal and pristane-induced inflammatory conditions. (b) Break point localization and motif targeting of Sμ–σδ junctions in the Sμ region (up to 1 kb from the 5′ primer). Arrows indicate the break point positions. Color bars represent the occurrences of relevant AID motifs (forward/reverse hotspots, WRCY (red)/RGYW (blue), palindromic switch hotspot AGCT (green) and cold spot GGG (magenta)). The location of the break points with these motifs is emphasized with a colored asterisk. Proportions of the identified break points on these motifs are represented in the bar graphs (same colors). Significance was assessed based on comparisons with random break positions. For each Sμ–σδ junction data set, N random positions were numerically drawn from the uniform distribution (0–1 kb), and motif co-localization was evaluated. Mean values over 10 000 simulations are reported in the bar graph, and the P-values of experimental versus random breaks were computed as the frequency of random events as extreme as experimental results. Motif targeting was significantly different (P = 0.0003, Fisher’sexact test) under basal and inflammatory conditions, as pristane-treated mice lost AGCT targeting in favor of break induction outside of canonical AID hotspots. (c) Break point localization and motif targeting of Sμ–σδ junctions along the σδ region (up to 1 kb from the 3′ primer). Breaks detected in the σδ region did not show a significant AID signature, with most of the break points detected outside AID motifs. Inflammatory conditions showed no significant differences in AID motif targeting in the σδ region compared with untreated mice (P = 0.43, Fisher’s exact test). pristane to determine whether enhanced the 3′RR super-enhancer. Furthermore, movens of CSR, which cis-regulatory IgH Sμ DNA double-strand breaks affected these results also show that μ–δ CSR is enhancer (if any) may be implicated in the structural profiles of IgD CSR. regulated and that double-strand breaks the control of IgD CSR? Clearly, the 3′RR Among 11 358 929 raw reads, 87 728 for Sμ–σδ CSR are not random breaks. super-enhancer that controls conven- reads were mapped to a switch junction, The structural profiles of IgD junctions tional CSR is not involved in this and the presence of 88 unique Sμ–σδ revealed a majority of junctions with particular IgH recombination. The IgH junctions was documented. As shown micro-homology or insertions compared intronic Eμ enhancer, previously in Figure 1a (right panel), the structural to blunt junctions, that is, a junctional reported to control VDJ recombination profiles of IgD junctions were signifi- pattern that markedly differs from IgG, but not CSR, might be an appropriate cantly affected in pristane-treated 3′RR- IgA and IgE CSR. Such junctional bias is candidate. Understanding the nature of deficient mice revealing less blunt strongly reminiscent of the junctions the transcriptional enhancer that acti- junctions and elevated junctions with produced by the alternative end-joining vates the regulation of IgD CSR remains micro-homology or insertions. Localiza- (A-EJ) pathway rather than the classical an exciting challenge. tions of break points were qualitatively non-homologous DNA end-joining (C- different in both Sμ (Figure 1b, right NHEJ) pathway used for IgG, IgA and CONFLICT OF INTEREST fl panel) and σδ (Figure 1c, right panel) in IgE CSR.9 These results are consistent The authors declare no con ict of interest.
Recommended publications
  • Mcb 407-Immunology and Immunochemistry-Lecture Note
    MCB 407-IMMUNOLOGY AND IMMUNOCHEMISTRY-LECTURE NOTE DR. D. A. OJO BRIEF HISTORICAL REVIEW OF IMMUNOLOGY The mechanism by which antibody are formed has been debated for years. It was proposed that the specificity of an antibody molecule was determined both by its amino acid sequence but by the molding of the peptide chain around the antigenic determinant. This theory lost favour when it became apparent that antibody-forming cells were devoid of antigen and that antibody specificity was a function of amino acid sequence. At present, the CLONAL (proposed by Burnete) SELECTION THEORY is widely accepted. It holds that an immunologically responsive cell can respond to only one antigen or a closely related group of antigens and that this property is inherent in the cell before the antigen is encountered. According to the clonal selection theory, each individual is endowed with a very large pool of lymphocytes, each of which is capable of responding to a different antigen. When the antigen enters the body, it selects the lymphocyte which has the best “fit” by virtue of a surface receptor. The antigen binds to this antibody-like receptor, and the cell is stimulated to proliferate and form a clone of cells. Thus, selected cells quickly differentiate into plasma cells and secrete antibody which is specific for the antigen which served as the original selecting agent (or a closely related group of antigens). The History of Blood Transfusion Man’s centuries-long desire to perform blood transfusion as a therapeutic procedure forms the cornerstone of the modern science of immunohematology. At present time, the use of whole blood is a well-accepted and commonly employed measure without which many modern surgical procedures could not be carried out.
    [Show full text]
  • A Challenging Case of Igd Kappa Multiple Myeloma Associated with Primary Amyloidosis: Importance of Serum Free Light Chains in M
    L al of euk rn em u i o a J Journal of Leukemia García de Veas Silva JL et al, J Leuk 2014, 2:5 ISSN: 2329-6917 DOI: 10.4172/2329-6917.1000164 Case Report Open Access A Challenging Case of IgD Kappa Multiple Myeloma Associated With Primary Amyloidosis: Importance of Serum Free Light Chains in Monitoring Treatment Response and Disease Relapse José Luis García de Veas Silva1*, Carmen Bermudo Guitarte1, Paloma Menéndez Valladares1, Rafael Duro Millán2 and Johanna Carolina Rojas Noboa2 1Department of Clinical Biochemistry, Hospital Universitario Virgen Macarena, Sevilla, Spain 2Department of Hematology, Hospital Universitario Virgen Macarena, Sevilla, Spain *Corresponding author: José Luis García de Veas Silva, Laboratory of Proteins, Department of Clinical Biochemistry, Hospital Universitario Virgen Macarena, Sevilla, Spain, Tel: +034955008108; E-mail: [email protected] Rec date: Oct 10, 2014, Acc date: Oct 16, 2014; Pub date: Oct 24, 2014 Copyright: © 2014 García de Veas Silva JL, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Multiple Myeloma (MM) is a malignancy of B cells characterized by an atypical proliferation of plasma cells. IgD MM has a very low incidence (2% of total MM cases) and it´s characterized by an aggressive course and a worse prognosis than other subtypes. The serum free light chains (sFLC) are very important markers for monitoring patients with MM and other monoclonal gammopathies. When the sFLC are present in low concentrations, it is often difficult to detect them by conventional methods such as serum protein electrophoresis and serum immunofixation.
    [Show full text]
  • Immunoglobulin D-Lambda Multiple Myeloma, and a Review of the Literature Aissam EL MAATAOUI*, Salma FARES and Aadil TAOUFIK
    ISSN: 2378-3656 MAATAOUI et al. Clin Med Rev Case Rep 2021, 8:341 DOI: 10.23937/2378-3656/1410341 Volume 8 | Issue 3 Clinical Medical Reviews Open Access and Case Reports CASE REPORT Immunoglobulin D-Lambda Multiple Myeloma, and a Review of the Literature Aissam EL MAATAOUI*, Salma FARES and Aadil TAOUFIK Faculty of Medicine and Pharmacy, Ibn Zohr University, Agadir, Morocco Check for updates *Corresponding author: Aissam EL MAATAOUI, Faculty of medicine and pharmacy, Ibn Zohr University, Agadir, Morocco MM. It is characterized by the high preponderance of Abstract lambda light chains over kappa light chains [3]. IgD multiple myeloma (MM) is a rare plasma cell neoplasm, considered to have a poor prognosis compared to the other Patients with IgD myeloma presented more often isotypes. Many studies reported an advanced stage at the with features of high-risk disease, that is, with advanced presentation. In contrast to these studies, we report a case ISS (International staging system), high LDH (lactate de- of rare IgD-Lambda MM at the early stage. The laboratory data showed no hypercalcemia, without any renal impair- hydrogenase), significant renal dysfunction, and large ment, or monoclonal spike (M-spike or paraprotein) at the amounts of Bence jones proteinuria [1,3]. Response to Serum protein electrophoresis (SEP) but only a hypogam- primary therapy was similar to other patients, although maglobulinemia. IF is performed with antisera to IgG, IgA, there was a trend for better quality of responses in pa- IgM, total kappa and total lambda(anti-γ, anti-α and an- ti-µ heavy chains, and anti-κ and anti-λ total light chains) tients with IgD myeloma [3].
    [Show full text]
  • Immunoglobulin D Enhances Interleukin-6 Release from the KU812 Human Prebasophil Cell Line
    Gen. Physiol. Biophys. (2003), 22, 255—263 255 Immunoglobulin D Enhances Interleukin-6 Release from the KU812 Human Prebasophil Cell Line B. Sechet1, A. Meseri-Delwail1,M.Arock2,J.Wijdenes3, J.-C. Lecron1 and D. Sarrouilhe1 1 Laboratoire Cytokines, FRE CNRS 2224, IBMIG, 40 avenue du Recteur Pineau, 86022 Poitiers Cedex, France 2 Laboratoire d’Hématologie Cellulaire, Faculté de Pharmacie, 4 avenue de l’observatoire, 75006 Paris, France 3 Diaclone, 1 boulevard Fleming, BP 1985, 25020 Besancon Cedex, France Abstract. Despite the role of secreted immunoglobulin D (IgD) remains still largely unknown, previous studies have suggested that secreted IgD could induce basophils degranulation in some allergic asthma patients. In the present study we have searched direct evidence of the action of IgD on KU812 cells, generally classified as an immature basophilic cell line. We analyzed by flow cytometry the capacity of IgD, purified from IgD myeloma sera, to bind KU812 cells. Biotiny- lated monomeric IgD (mIgD) and biotinylated oligomeric IgD (oIgD) could bind KU812 cells. Blocking experiments with others immunoglobulin isotypes showed that KU812 cells expressed an unspecific receptor for IgD. However, oIgD but not mIgD enhances the release of interleukin-6 (IL-6) from KU812 cells. On the other hand, mIgD and oIgD failed to induce histamine release from KU812 cells or from cord blood derived basophils. Since IL-6 is known to induce basophil differentiation, we proposed that IgD could be implicated in allergic disorders by stimulating IL-6 release by prebasophil cells, then IL-6 could further induce an autocrine maturation of the cells. Key words: Immunoglobulin D — Prebasophil — Interleukin-6 — Flow cytometry — Histamine Introduction Since the discovery of immunoglobulin D (IgD) in 1965, studies have mainly been focused on membrane IgD which is a major component of the B cell antigen receptor (BCR).
    [Show full text]
  • Immunoglobulin D Undergoes Placental Transfer to the Fetus
    Wayne State University Wayne State University Theses January 2019 Immunoglobulin D Undergoes Placental Transfer To The Fetus Michael David Pawlitz Wayne State University, [email protected] Follow this and additional works at: https://digitalcommons.wayne.edu/oa_theses Part of the Immunology and Infectious Disease Commons Recommended Citation Pawlitz, Michael David, "Immunoglobulin D Undergoes Placental Transfer To The Fetus" (2019). Wayne State University Theses. 716. https://digitalcommons.wayne.edu/oa_theses/716 This Open Access Embargo is brought to you for free and open access by DigitalCommons@WayneState. It has been accepted for inclusion in Wayne State University Theses by an authorized administrator of DigitalCommons@WayneState. IMMUNOGLOBULIN D UNDERGOES PLACENTAL TRANSFER TO THE FETUS by MICHAEL DAVID PAWLITZ THESIS Submitted to the Graduate School of Wayne State University, Detroit, Michigan in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE 2019 MAJOR: IMMUNOLOGY & MICROBIOLOGY Approved By: _____________________________________ Advisor Date © COPYRIGHT BY MICHAEL DAVID PAWLITZ 2019 All Rights Reserved ACKNOWLEDGMENTS There are plenty individuals in my life that deserve to be acknowledged for their support during the pursuit of my graduate studies. First and foremost, I would like to thank my mentor, Dr. Kang Chen, who has been a superlative role model to me. He has provided me with phenomenal insight throughout the entirety of my research project. I cannot thank him enough for all his time and effort that was devoted towards my graduate studies. Additionally, I would like to thank all members of the Chen lab, past and present, who have also taught me and helped me along the way to become a better researcher.
    [Show full text]
  • 4 Antibodies from Other Species Melissa L
    85 4 Antibodies from Other Species Melissa L. Vadnais1, Michael F. Criscitiello2, and Vaughn V. Smider1 1Department of Molecular Medicine, The Scripps Research Institute, 10550 N. Torrey Pines, La Jolla, CA 92037, USA 2Texas A&M University, College of Veterinary Medicine and Biomedical Sciences, Department of Veterinary Pathobiology, 400 Raymond Stotzer Parkway, College Station, TX 77843, USA 4.1 Introduction Immunoglobulins are the molecular basis of humoral immunity. Across different species, these macromolecules maintain a common quaternary structure, which is typically comprised of two identical heavy chains with covalently attached oligosaccharide groups and two identical non-glycosylated, light chains. These glycoprotein molecules recognize and bind a particular antigen in a highly complex and exceedingly specific immune response. Antibodies are the primary protective molecules elicited by most vaccines, and recombinant antibodies are now a major class of therapeutics for multiple diseases. The earliest antibody therapeutics were derived from serum of nonhuman species. In particular, horse serum served as anti-venom yet had substantial toxicity (serum sickness) due totheimmuneresponseagainstthenonhumanantibodyprotein[1,2].Other antibody preparations such as anti-thymocyte globulin produced in rabbit had therapeutic benefit but also had significant toxicity. The use of alternative species for these therapeutic preparations was largely due to ease of production, as they were developed prior to the advent of modern molecular biology techniques, which have enabled rapid discovery and engineering of recombinant antibodies. Thus, most current approaches for producing recombinant antibodies rely on humanizing antibodies derived from other species, usually mice, or beginning with human scaffolds engineered into libraries or transgenic “humanized” mice. Recently, however, novel features of antibodies derived from other species have sparked interest in developing antibodies that may have particular unique features in binding certain antigens or epitopes [3–7].
    [Show full text]
  • Insights Into the Function of Igd
    Developmental and Comparative Immunology 35 (2011) 1309–1316 Contents lists available at ScienceDirect Developmental and Comparative Immunology journal homepage: www.elsevier.com/locate/dci Insights into the function of IgD Eva-Stina Edholm, Eva Bengten, Melanie Wilson ∗ University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, United States article info abstract Article history: IgD, previously thought to be a recent addition to the immunoglobulin classes, has long been consid- Available online 15 March 2011 ered an enigmatic molecule. For example, it was debated if IgD had a specific function other than as an antigen receptor co-expressed with IgM on naive B cells and if it had an important role in mammalian Keywords: immunity. However, during the past decade extensive sequencing of vertebrate genomes has shown that Teleosts IgD homologs are present in all vertebrate taxa, except for birds. Moreover, recent functional studies Immunoglobulin indicate that IgD likely performs a unique role in vertebrate immune responses. The goal of this review is IgD to summarize the IgD gene organization and structural data, which demonstrate that IgD has an ancient Alternative splicing B cells origin, and discuss the findings in catfish and humans that provide insight into the possible function of this elusive immunoglobulin isotype. © 2011 Elsevier Ltd. All rights reserved. 1. Introduction (Gambon-Deza et al., 2010), and Atlantic salmon, Salmo salar (Tadiso et al., 2010). However, PCR and genomic sequencing stud- It is well
    [Show full text]
  • Metabolism of Human Immunoglobulin D (Igd)
    Journal of Clinical Investigation Vol. 45, No. 9, 1966 Metabolism of Human Immunoglobulin D (IgD) * G. NICHOLAS ROGENTINE, JR.,t DAVID S. ROWE, JOHN BRADLEY, THOMAS A. WALDMANN, AND JOHN L. FAHEY (From the Immunology Branch and Metabolism Service, National Cancer Institute, National Institutes of Health, Bethesda, Md., and the Department of Experimental Pathology, The Medical School, University of Birmingham, Birmingham, England) In addition to the three commonly recognized tration and that IgD is metabolized independently classes of human immunoglobulins (IgG, IgA, and of the other immunoglobulins. IgM), a fourth immunoglobulin class was recently identified and designated IgD (yD) (1, 2). Se- Methods rum values in normal subjects ranged from less Preparation of labeled IgD. IgD was isolated from than 3 ug to greater than 100 /Ag IgD per ml of whole human serum or plasma by DEAE cellulose chro- serum (2). The median serum IgD concentration matography followed by Sephadex G-200 gel filtration was 30 Mg per ml, about 1/, o of the serum IgG according to the method of Rowe and Fahey (2). concentration. IgD is the least plentiful member Two separate studies were done with radioiodine- of the immunoglobulin family. labeled IgD. Different sources of IgD were used for each study; therefore, the preparation and characteriza- The immunoglobulin system is interesting from tion of the labeled purified proteins will be discussed a metabolic standpoint. The biological half-life of separately. normal IgG is about 23 days and its synthetic rate IgD preparation no. 1. This protein was prepared from 40 mg per kg per day (3, 4).
    [Show full text]
  • Immunology and Serology
    LECTURE NOTES For Medical Laboratory Technology Students Immunology and Serology Selamawit Debebe Alemaya University In collaboration with the Ethiopia Public Health Training Initiative, The Carter Center, the Ethiopia Ministry of Health, and the Ethiopia Ministry of Education 2004 Funded under USAID Cooperative Agreement No. 663-A-00-00-0358-00. Produced in collaboration with the Ethiopia Public Health Training Initiative, The Carter Center, the Ethiopia Ministry of Health, and the Ethiopia Ministry of Education. Important Guidelines for Printing and Photocopying Limited permission is granted free of charge to print or photocopy all pages of this publication for educational, not-for-profit use by health care workers, students or faculty. All copies must retain all author credits and copyright notices included in the original document. Under no circumstances is it permissible to sell or distribute on a commercial basis, or to claim authorship of, copies of material reproduced from this publication. ©2004 by Selamawit Debebe All rights reserved. Except as expressly provided above, no part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or by any information storage and retrieval system, without written permission of the author or authors. This material is intended for educational use only by practicing health care workers or students and faculty in a health care field. Immunology and Serology Preface Immunology and serology is an advanced science dealing with how the human immune system organized, function and the different types of serological techniques. It is a very vast subject covering a wide area of technology.
    [Show full text]
  • An Extremely Rare Manifestation of Multiple Myeloma: an Immunoglobulin D Secreting Testicular Plasmacytoma
    Open Access Case Report DOI: 10.7759/cureus.1400 An Extremely Rare Manifestation of Multiple Myeloma: An Immunoglobulin D Secreting Testicular Plasmacytoma Ashish Sharma 1 , Tina Binazir 1 , Alexandre Sintow 1 , Chi Chan Lee 1 , Sameer Shaharyar 1 , Jason Tache 2 1. Internal Medicine, Aventura Hospital and Medical Center 2. Oncology, Westside Regional Medical Center Corresponding author: Tina Binazir, [email protected] Abstract Multiple myelomas (MM) of the immunoglobulin D (IgD) subtype is rare amongst plasma cell malignancies. It can present a diagnostic challenge because of the low amount of immunoglobulin in the serum. The amount of monoclonal (M)-protein is often undetectable on electrophoresis. Historically, survival in these patients was typically shorter compared to the immunoglobulin A (IgA) and immunoglobulin G (IgG) subtypes due to advanced disease upon presentation. With the advent of better diagnostic techniques, the prognosis of this disease is changing. We describe a case of an extramedullary testicular plasmacytoma (EMP) of the IgD subtype as the primary feature of MM, which responded well to novel therapy. A 72-year-old White male presented to the emergency room with a right testicular mass for three months. He subsequently underwent right radical orchiectomy. Pathology of the specimen revealed plasmacytoid cells positive for cluster of differentiation (CD79a), lambda free light chain, IgD, and BCL-1 (Cyclin D1) on immunochemical stains. Urine and serum immunofixation were positive for monoclonal IgD with lambda light chain specificity and Bence Jones proteinuria. Bone marrow biopsy showed large sheets of plasma cells with greater than 90% cellularity. Flow cytometry displayed atypical plasma cells expressing cluster of differentiation (CD38, CD20, and CD56) with cytoplasm and lambda light chain, approximately 20%, consistent with a plasma cell dyscrasia.
    [Show full text]
  • UNDERSTANDING YOUR MULTIPLE MYELOMA LAB TESTS This Lab Tracker Booklet Explains Common Tests for Patients with Multiple Myeloma
    UNDERSTANDING YOUR MULTIPLE MYELOMA LAB TESTS This lab tracker booklet explains common tests for patients with multiple myeloma. If you have any questions about your test results, discuss them with your healthcare team. LAB TEST TRACKER This worksheet can serve as a personal record of your lab test results. Reference ranges— values that are considered normal in healthy individuals—are provided below as guides. Note that ranges vary among laboratories. Date of laboratory test Mark the test values in the Reference ranges column below each date COMPLETE BLOOD COUNT (CBC)1,2 Pages 4-5 White blood cells (WBCs) 3.5-10.5 2 109/L Neutrophils 1.56-6.45 2 109/L Males: 4.32-5.72 2 1012/L Red blood cells (RBCs) Females: 3.90-5.03 2 1012/L Males: 38.8%-50.0% Hematocrit Females: 34.9%-44.5% Males: 13.5-17.5 g/dL Hemoglobin (Hgb) Females: 12.0-15.5 g/dL Platelets 150-450 2 109/L CHEMISTRY PROFILE3–8 Pages 6-8 Blood urea nitrogen (BUN), serum 7-20 mg/dL Males: 0.74-1.35 mg/dL Creatinine, serum Females: 0.59-1.04 mg/dL Calcium, total, serum 8.8-10.2 mg/dL Glucose, serum (fasting) ≤126 mg/dL Protein, total, serum 6.3-7.9 g/dL Beta2-microglobulin (B2M), serum 1.21-2.70 mcg/mL SERUM PROTEIN ELECTROPHORESIS (SPEP)9 Pages 8-9 Any M spike presence M spike (myeloma gamma globulin) may be abnormal Unit measures: dL=A deciliter is equal to one tenth of a liter; g=A gram is a unit of measurement of mass, or the total amount of matter in an object; L=A liter is a unit of measurement of volume.
    [Show full text]
  • A Protean Protein
    CLINICAL CARE CONUNDRUM A Protean Protein Mariam T Nawas, MD1*; Evan J Walker, MD2; Megan B Richie, MD3; Andrew A White, MD4; Gerald Hsu, MD, PhD2 This icon represents the patient’s case. Each paragraph that follows represents the discussant’s thoughts. 1Medical Oncology Fellowship Program, Memorial Sloan-Kettering Cancer Center, New York, New York; 2Department of Medicine, University of California, San Francisco Medical Center, San Francisco, California; 3Department of Neurology, University of California, San Francisco Medical Center, San Francisco, California; 4Department of Medicine, University of Washington Medical Center, Seattle, Washington. A 39-year-old man presented to a neurologist with three Electromyography and nerve conduction studies re- weeks of progressive leg weakness associated with vealed a sensorimotor mixed axonal/demyelinating numbness in his feet and fingertips. His medical history in- polyneuropathy in all extremities. CSF analysis found one cluded hypertriglyceridemia, hypogonadism, and gout. He white cell per mm3, glucose of 93 mg/dL, and protein of 313 was taking fenofibrate and colchicine as needed. There was mg/dL. Magnetic resonance imaging (MRI) of the spine with- no family history of neurologic issues. He did not smoke or out contrast showed normal cord parenchyma. The vitamin drink alcohol. B12 level was 441 pg/mL (normal >200 pg/mL). Antibodies to The patient appeared well with a heart rate of 76 beats per HIV-1, HIV-2, hepatitis C virus, and Borrelia burgdorferi were minute, blood pressure 133/72 mm Hg, temperature 36.6°C, negative. Serum protein electrophoresis (SPEP) and immuno- respiratory rate 16 breaths per minute, and oxygen satura- fixation were normal.
    [Show full text]